Relation of serum vascular endothelial growth factor as an angiogenesis biomarker with nitric oxide & urokinase-type plasminogen activator in breast cancer patients.

BACKGROUND & OBJECTIVE The primary mediator of angiogenesis is vascular endothelial growth factor (VEGF). It is well documented that angiogenic activity in human cancer depends on nitric oxide (NO) levels in tissues. Additionally, urokinase type plasminogen activator (u-PA) plays a role in cell adhesion and migration. Serum VEGF and its relationship between NO and u-PA concentrations are poorly reported in breast cancer patients. The aim of this study was to investigate the relationship between serum levels of VEGF and NO and u-PA in patients with breast cancer. METHODS Serum concentrations of VEGF, NO and u-PA were measured in groups of pre-operative breast cancer patients without metastasis (n=20), post-operative breast cancer patients without metastasis (four wk after the operation, n=20), breast cancer patients with metastasis (n=23), patients with benign breast disease (n=11) and healthy female controls (n=20). RESULTS There was no difference in serum concentrations of VEGF, NO and u-PA between controls and patients with benign breast disease. Serum VEGF, NO and u-PA concentrations were significantly higher in pre-operative breast cancer patients than in controls and in patients with benign breast diseases (P<0.01). Post-operative breast cancer patients without metastasis had significantly lower serum VEGF and u-PA concentrations than the pre-operative patients (P<0.01). In breast cancer patients with metastasis, serum VEGF, and u-PA were significantly higher than post-operative nonmetastatic patients (P<0.01). Serum VEGF concentrations were positively correlated with serum uPA in all of the patients groups (r=0.886, P<0.01). Serum VEGF levels were positively correlated with serum NO levels in breast cancer patients with metastasis (r= 0.386, P<0.05). INTERPRETATION & CONCLUSION Our results demonstrated that the angiogenic activity was increased in patients with breast cancer. Elevated VEGF levels as an angiogenesis marker may be associated with uPA. VEGF, NO and uPA seem to be associated with the angiogenetic and metastatic process of breast cancer.